Measurement Of Left Ventricular Pressure Research Articles

MRI-based finite-element analysis of left ventricular aneurysm

Tagged MRI and finite-element (FE) analysis are valuable tools in analyzing cardiac mechanics. To determine systolic material parameters in three-dimensional stress-strain relationships, we used tagged MRI to validate FE models of left ventricular (LV) aneurysm. Five sheep underwent anteroapical myocardial infarction (25% of LV mass) and 22 wk later underwent tagged MRI. Asymmetric FE models of the LV were formed to in vivo geometry from MRI and included aneurysm material properties measured with biaxial stretching, LV pressure measurements, and myofiber helix angles measured with diffusion tensor MRI. Systolic material parameters were determined that enabled FE models to reproduce midwall, systolic myocardial strains from tagged MRI (630 +/- 187 strain comparisons/animal). When contractile stress equal to 40% of the myofiber stress was added transverse to the muscle fiber, myocardial strain agreement improved by 27% between FE model predictions and experimental measurements (RMS error decreased from 0.074 +/- 0.016 to 0.054 +/- 0.011, P < 0.05). In infarct border zone (BZ), end-systolic midwall stress was elevated in both fiber (24.2 +/- 2.7 to 29.9 +/- 2.4 kPa, P < 0.01) and cross-fiber (5.5 +/- 0.7 to 11.7 +/- 1.3 kPa, P = 0.02) directions relative to noninfarct regions. Contrary to previous hypotheses but consistent with biaxial stretching experiments, active cross-fiber stress development is an integral part of LV systole; FE analysis with only uniaxial contracting stress is insufficient. Stress calculations from these validated models show 24% increase in fiber stress and 115% increase in cross-fiber stress at the BZ relative to remote regions, which may contribute to LV remodeling.

Myocardial Acceleration During Isovolumic Contraction

Acceleration of the mitral ring during isovolumic contraction has been proposed as a load-independent index of global left ventricular (LV) contractility. This study investigates whether myocardial isovolumic acceleration (IVA) reflects regional contractility. In acutely instrumented, anesthetized dogs, we measured LV pressure, myocardial long-axis velocities, and IVA by tissue Doppler imaging (TDI) and sonomicrometry at different levels of global LV contractility and preload and during regional myocardial ischemia (reduced flow in the left anterior descending coronary artery). Dobutamine caused dose-dependent increments in IVA from 3.6+/-0.6 (mean+/-SEM) to a maximum of 7.1+/-1.4 m/s2 (P<0.01) by TDI, and there were parallel increments in LV dP/dt(max) (P<0.01). However, volume loading decreased IVA from 3.6+/-0.6 to 2.5+/-0.4 m/s2 (P<0.05), whereas LV dP/dt(max) was unchanged, and LV pressure-segment length loop analysis confirmed unchanged regional contractility. During myocardial ischemia, sonomicrometry indicated severely depressed regional function, whereas IVA remained unchanged. These findings were confirmed when IVA was measured by sonomicrometry. In contrast to peak ejection velocity that increased from apex toward the LV base, peak IVC velocity was maximum midway between apex and base. The onset of IVA coincided with onset of the first heart sound by phonocardiography. Peak IVA occurred at a LV pressure of 14+/-1 mm Hg, ie, close to end-diastole. There was no consistent relationship between peak IVA and regional myocardial contractility. Peak IVA was markedly load dependent and did not reflect impaired myocardial function during ischemia. Peak IVA may reflect late-diastolic events and possibly wall oscillations that are related to global LV function. Peak IVA seems to have limited potential in the assessment of regional myocardial function.

Acute Hemodynamic Benefit of Left Ventricular Apex Pacing in Children

Despite the fact that pacing at the right ventricular apex acutely and chronically decreases left ventricular contractile function, this pacing site is still conventionally used in adults and children. Because animal studies showed beneficial effects of left ventricular pacing, we compared the hemodynamic performance of left ventricular apex, left ventricular free wall, and right ventricular apex pacing in children. Studies were performed in 10 children (median age, 2.5 years; range, 2 months to 17 years) undergoing surgery for congenital heart disease with normal systemic left ventricular anatomy and intraventricular conduction. High-fidelity left ventricular and arterial pressure measurements were performed during epicardial right ventricular apex and left ventricular apex and free wall pacing. Left ventricular apex pacing increased the maximum rate of rise of left ventricular pressure and pulse pressure significantly relative to right ventricular apex pacing (by 7.7% +/- 7.2% and 7.7% +/- 7.0%, respectively) without changes in end-diastolic left ventricular pressure. Left ventricular free wall pacing did not significantly improve hemodynamics as compared with right ventricular apex pacing. The QRS duration was not different among pacing at the three sites. In this short-term study left ventricular apex pacing is hemodynamically superior to right ventricular apex and left ventricular free wall pacing in children. Therefore, the left ventricular apex appears a favorable pacing site after pediatric cardiac surgery.

Plasma levels of N-terminal pro-brain natriuretic peptide in patients with coronary artery disease and relation to clinical presentation, angiographic severity, and left ventricular ejection fraction

Comparative assessment of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) across a wide spectrum of angiographic and clinical coronary artery disease (CAD) in a consecutive series of patients has not been reported. This study examined 879 subjects (684 patients who had angiographically proved CAD and 195 controls who did not have CAD). NT-pro-BNP concentrations were measured before an angiographic procedure that allowed diagnosis of CAD and measurements of left ventricular ejection fraction and end-diastolic blood pressure. Median values (25th and 75th percentiles) of NT-pro-BNP in patients and controls were 474.5 pg/ml (162.3 and 1,542.8) and 117.0 pg/ml (60.1 and 230.6), respectively (p <0.001). In patients who had stable angina, unstable angina, and acute myocardial infarction, NT-pro-BNP concentrations were 327.7 pg/ml (129.2 and 973.2), 660.6 pg/ml (201.2 and 1,563.5), and 1,045.0 pg/ml (323.8 and 2,486.0, p <0.001). NT-pro-BNP concentrations in subgroups with 1-, 2-, and 3-vessel CAD were 385.5 pg/ml (117.2 and 1,266.0), 463.0 pg/ml (135.0 and 1,480.5), and 533.8 pg/ml (221.8 and 1,809.4), respectively (p = 0.005). Multivariable analysis showed that NT-pro-BNP was an independent correlate of the presence of CAD (chi-square 10.8, odds ratio 1.08, 95% confidence interval 1.03 to 1.13 for 100-pg/ml increase in concentration; p <0.001), acute coronary syndromes (chi-square 6.3, odds ratio 1.01, 95% confidence interval 1.00 to 1.02 for 100-pg/ml increase in concentration, p = 0.01) and a strong trend that was independently associated with angiographic severity (chi-square 3.68, p = 0.055). This study shows that NT-pro-BNP concentrations are high across the entire spectrum of CAD and parallel the clinical or angiographic severity of CAD.

Positive inotropic effect of nicorandil in adult rats in situ

Although the cardiac protective and negative inotropic effects of nicorandil via opening the sarcolemmal or mitochondrial K(ATP) channel and NO-like action are well known, positive inotropic effects of nicorandil in normal hearts have not been reported. The aim of the current study was to investigate how nicorandil affects left ventricular (LV) function of in situ adult rat hearts through the entire cardiovascular system. We performed simultaneous and continuous measurements of LV pressure (P) by a catheter-tip micromanometer and LV volume (V) using a conductance catheter. We obtained steady-state LV P-V loops and intermittent curvilinear LV end-systolic pressure-volume relations (ESPVRs), LV end-systolic pressure (ESP(mLVV)), and systolic pressure-volume area (PVA(mLVV)) at midrange LVV (mLVV). We evaluated the effects of nicorandil on LV function by these mechanical indexes sensitively reflecting changes in LV contractility and work capability, preload (end-diastolic volume, EDV), and afterload (effective arterial elastance, Ea). Nicorandil (10 and 20 microg.kg(-1).min(-1)) (blood concentration: 0.53 +/- 0.14 and 1.48 +/- 0.21 microg/ml) largely shifted ESPVR upward and thus significantly increased ESP(0.06), PVA(0.06), stroke volume due to increase in EDV, and ejection fraction without significant changes in Ea and heart rate. In contrast, an NO donor, nitroglycerin (1 microg.kg(-1) . min(-1)), significantly decreased Ea but did not change ESP(0.06), PVA(0.06), and EDV. Furthermore, either a nonselective K(ATP) channel blocker, glybenclamide, or a mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, abolished these nicorandil-induced positive inotropic actions. These results suggest that nicorandil exhibited positive inotropic actions on LV function of in situ hearts in adult rats with resultant increased preload (EDV).

Interventricular Septal Configuration at MR Imaging and Pulmonary Arterial Pressure in Pulmonary Hypertension

To investigate whether a relationship exists between septum shape and systolic pulmonary arterial pressure (PAP) in patients with pulmonary hypertension. Study protocol was approved by institutional ethics review committee; all patients gave informed consent. Right-sided heart catheterization with vasodilator testing was performed in 39 adult subjects suspected of having pulmonary hypertension. There were 11 men and 28 women, aged 21-75 years (mean, 46 years). Only two patients showed favorable response to vasodilators, defined by a decrease in PAP of more than 20%. Synchronous right- and left-ventricular pressure measurements and four-chamber magnetic resonance (MR) imaging were used to identify timing of maximal leftward ventricular septal bowing within cardiac cycle. Septal bowing was evaluated with MR, measured on short-axis cine heart images, and expressed as curvature (reciprocal of radius). Curvature was quantified on one image (the one that showed the most severe distortion of normal septal shape). The relationship between systolic PAP and septal curvature was tested with linear regression analysis. P <.05 was considered to indicate a statistically significant difference. Of 39 subjects, 37 had pulmonary hypertension. Maximal distortion of normal septal shape was found during right ventricular relaxation phase. Systolic PAP was proportional to septal curvature: r=0.77 (P < .001), slope=-114.7, and intercept=67.2. In the two vasodilator responsive subjects, a significant reduction of leftward ventricular septal bowing was observed in response to reduction of right ventricular pressure. In 37 patients with pulmonary hypertension, systolic PAP higher than 67 mm Hg may be expected when leftward curvature is observed.

Human Umbilical Cord Blood Mononuclear Cells for the Treatment of Acute Myocardial Infarction

Cell transplantation is a new treatment to improve cardiac function in hearts that have been damaged by myocardial infarction. We have investigated the use of human umbilical cord blood mononuclear progenitor cells (HUCBC) for the treatment of acute myocardial infarction. The control group consisted of 24 normal rats with no interventions. The infarct + vehicle group consisted of 33 rats that underwent left anterior descending coronary artery (LAD) ligation and after 1 h were given Isolyte in the border of the infarction. The infarct + HUCBC group consisted of 38 rats that underwent LAD ligation and after 1 h were given 10(6) HUCBC in Isolyte directly into the infarct border. Immunosuppression was not given to any rat. Measurements of left ventricular (LV) ejection fraction, LV pressure, dP/dt, and infarct size were determined at baseline and 1, 2, 3, and 4 months. The ejection fraction in the controls decreased from 88+/-3% to 78+/-4% at 4 months (p = 0.03) as a result of normal aging. Following infarction in the infarct + vehicle group, the ejection fraction decreased from 87+/-4% to 51+/-3% between 1 and 4 months (p < 0.01). In contrast, the ejection fraction of the infarcted + HUCBC-treated rat hearts decreased from 87+/-4% to 63+/-3% at 1 month, but progressively increased to 69+/-6% at 3 and 4 months, which was different from infarct + vehicle group rats (p < 0.02) but similar to the controls. At 4 months, anteroseptal wall thickening in infarct + HUCBC group was 57.9+/-11.6%, which was nearly identical to the control anteroseptal thickening of 59.2+/-8.9%, but was significantly greater than the infarct + vehicle group, which was 27.8+/-7% (p < 0.02). dP/dt(max) increased by 130% in controls with 5.0 microg of phenylephrine (PE)/min (p < 0.001). In the infarct + vehicle group, dP/dt(max) increased by 91% with PE (p = 0.01). In contrast, in the infarct + HUCBC group, dP/dt(max) increased with PE by 182% (p < 0.001), which was significantly greater than the increase in dP/dt(max) in the infarct + vehicle group (p = 0.03) and similar to the increase in the controls. Infarct sizes in the infarct + HUCBC group were smaller than the infarct + vehicle group and averaged 3.0+/-2.8% for the infarct + HUCBC group versus 22.1+/-5.6% for infarct + vehicle group at 3 months (p < 0.01); at 4 months they averaged 9.2+/-2.0% for infarct + HUCBC group versus 40.0+/-9.2% for the infarct + vehicle group (p < 0.001). The present experiments demonstrate that HUCBC substantially reduce infarction size in rats without requirements for immunosuppression. As a consequence, LV function measurements, determined by LV ejection fraction, wall thickening, and dP/dt, are significantly greater than the same measurements in rats with untreated infarctions.

Inhibition of PLC improves postischemic recovery in isolated rat heart.

The Ca2+-dependent PLC converts phosphatidylinositol 4,5-bisphosphate to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Because these products modulate Ca2+ movements in the myocardium, PLC may also contribute to a self-perpetuating cycle that exacerbates cardiomyocyte Ca2+-overload and subsequent cardiac dysfunction in ischemia-reperfusion (I/R). Although we have reported that I/R-induced changes in PLC isozymes might contribute to cardiac dysfunction, the present study was undertaken to examine the beneficial effects of the PLC inhibitor, U-73122, as well as determining the role of Ca2+ on the I/R-induced changes in PLC isozymes. Isolated rat hearts were subjected to global ischemia 30 min, followed by 5 or 30 min of reperfusion. Pretreatment of hearts with U-73122 (0.5 microM) significantly inhibited DAG and Ins(1,4,5)P3 production in I/R and was associated with enhanced recovery of cardiac function as indicated by measurement of left ventricular (LV) end-diastolic pressure (EDP), LV diastolic pressure (LVDP), maximum rate of pressure development (+dP/dtmax), and maximum rate of LV pressure decay (-dP/dtmax). Verapamil (0.1 microM) partially prevented the increase in sarcolemmal (SL) PLC-beta1 activity in ischemia and the decrease in its activity during the reperfusion phase as well as elicited a partial protection of the depression in SL PLC-delta1 and PLC-gamma1 activities during the ischemic phase and attenuated the increase during the reperfusion period. Although these changes were associated with an improved myocardial recovery after I/R, verapamil was less effective than U-73122. Perfusion with high Ca2+ resulted in the activation of the PLC isozymes studied and was associated with a markedly increased LVEDP and reduced LVDP, +dP/dtmax, and -dP/dtmax. These results suggest that inhibition of PLC improves myocardial recovery after I/R.

Role of tyrosine kinase in desflurane-induced preconditioning.

Short administration of volatile anesthetics preconditions myocardium and protects the heart against the consequences of subsequent ischemia. Activation of tyrosine kinase is implicated in ischemic preconditioning. The authors investigated whether desflurane-induced preconditioning depends on activation of tyrosine kinase. Sixty-four rabbits were instrumented for measurement of left ventricular pressure, cardiac output, and myocardial infarct size (IS). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits underwent a treatment period consisting of either no intervention for 35 min (control group, n = 12) or 15 min of 1 minimum alveolar concentration desflurane inhalation followed by a 10-min washout period (desflurane group, n = 12). Four additional groups received the tyrosine kinase inhibitor genistein (5 mg/kg) or lavendustin A (1.3 mg/kg) at the beginning of the treatment period with (desflurane-genistein group, n = 11; desflurane-lavendustin A group, n = 12) or without desflurane inhalation (genistein group, n = 9; lavendustin A group, n = 8). Hemodynamic values were similar in all groups during baseline (left ventricular pressure, 87 +/- 14 mmHg (mean +/- SD]; cardiac output, 198 +/- 47 ml/min), during coronary artery occlusion (left ventricular pressure, 78 +/- 12 mmHg; cardiac output, 173 +/- 39 ml/min), and after 2 h of reperfusion (left ventricular pressure, 59 +/- 17; cardiac output, 154 +/- 43 ml/min). IS in the control group was 55 +/- 10% of the area at risk. The tyrosine inhibitors had no effect on IS (genistein group, 56 +/- 13%; lavendustin A group, 49 +/- 13%; each P = 1.0 vs. control group). Desflurane preconditioning reduced IS to 40 +/- 15% (P = 0.04 vs. control group). Tyrosine kinase inhibitor administration had no effect on IS reduction (desflurane-genistein group, 44 +/- 13%; desflurane-lavendustin A group, 44 +/- 16%; each P = 1.0 vs. desflurane group). Desflurane-induced preconditioning does not depend on tyrosine kinase activation.

Noninvasive estimation of left ventricular filling pressure by e/e′ is a powerful predictor of survival after acute myocardial infarction

ObjectivesThe aim of this study was to assess the prognostic value of a noninvasive measure of left ventricular diastolic pressure (LVDP) early after acute myocardial infarction (MI). BackgroundThe early diastolic velocity of the mitral valve annulus (e′) reflects the rate of myocardial relaxation. When combined with measurement of the early transmitral flow velocity (E), the resultant ratio (E/e′) correlates well with mean LVDP. In particular, an E/e′ ratio >15 is an excellent predictor of an elevated mean LVDP. We hypothesized that an E/e′ ratio >15 would predict poorer survival after acute MI. MethodsEchocardiograms were obtained in 250 unselected patients 1.6 days after admission for MI. Patients were followed for a median of 13 months. The end point was all-cause mortality. ResultsSeventy-three patients (29%) had an E/e′ >15. This was associated with excess mortality (log-rank statistic 21.3, p < 0.0001) and was the most powerful independent predictor of survival (risk ratio 4.8, 95% confidence interval 2.1 to 10.8, p = 0.0002). The addition of E/e′ >15 improved the prognostic utility of a model containing clinical variables and conventional echocardiographic indexes of left ventricular systolic and diastolic function (p = 0.001). ConclusionsE/e′ is a powerful predictor of survival after acute MI. An E/e′ ratio >15 is superior, in this respect, to other clinical or echocardiographic features. Furthermore, it provides prognostic information incremental to these parameters.

Influence of isoflurane on left atrial function in dogs with pacing-induced cardiomyopathy: evaluation with pressure-volume relationships

Objective The actions of volatile anesthetics on left ventricular (LV) function in normal and failing hearts have been previously evaluated, but the effects of these agents on left atrial (LA) function in the presence of LV dysfunction are unknown. The hypothesis was tested that isoflurane alters LA mechanics evaluated with pressure-volume relations. Design Prospective. Setting Laboratory. Participants Barbiturate-anesthetized dogs (n = 8) were instrumented for measurement of aortic, LA, and LV pressures (micromanometers), and LA volume (epicardial orthogonal sonomicrometers) after 3 weeks of rapid ventricular pacing (220 beats/min). Interventions LA myocardial contractility (E es) was assessed with end-systolic pressure-volume relations. LA stroke work and reservoir function were assessed by A and V loop area, respectively, from the steady-state pressure-volume diagram. LA-LV coupling was determined by the ratio of E es to LV elastance (E LV). Dogs received 0.6, 0.9, and 1.2 minimum alveolar concentration isoflurane in a random manner, and LA function was determined after a 20-minute equilibration at each dose. Measurements and main results Isoflurane significantly ( p < 0.05) decreased heart rate, mean arterial pressure, LV end-systolic pressure, and LV +dP/dt max. Isoflurane produced dose-related reductions in E es and E es/E LV. Declines in LA stroke work, emptying fraction, reservoir volume, V loop area, and the active LA contribution to LV filling also occurred. Conclusions The results indicate that isoflurane depresses LA myocardial contractility, impairs LA-LV coupling, and reduces active LA contribution to LV filling in dogs with pacing-induced cardiomyopathy. The impact of isoflurane on LA function in the presence of LV dysfunction has profound effects on cardiac performance.

Evidence for an intracellular site of action in the heart for two hydrophobic cardiac steroids

Although cardiac steroids (CS) have long been used to treat cardiac insufficiency, the mechanism(s) of action of these agents remain open to question. While many results indicate that inhibition of Na +,K +-ATPase underlies both the therapeutic and toxic actions of CS, other studies suggest that actions on the SR membrane system may be important. We used two experimental approaches and measurements of left ventricular diastolic pressure (LVDP) in isolated guinea pig hearts to test whether CS had an intracellular site of action. In the first approach, we compared the inotropic effects of a hydrophilic CS, ouabain, and a hydrophobic CS, digitoxin, after the activity of the Na + pump was reduced by perfusing hearts with solutions maintained at 5°C. Under these conditions, exposure of hearts to 1 μM ouabain for 60 min did not increase LVDP above control levels. In contrast, an equi-effective concentration of digitoxin (0.3 μM) increased LVDP by 40 ± 8.5% (p<0.01) over pre-drug control levels. In the second experimental approach, we compared the inotropic effects of ouabain and digitoxin in the presence of rapid-cooling contractures (RCC), which result in the release of SR Ca 2+. Hearts were perfused with Tyrode solution or Tyrode solution containing either digitoxin (0.3 μM) or ouabain (1 μM) for 180 sec, rapidly cooled and the RCC responses were analyzed. Compared to RCC elicited in Tyrode solution alone, or in Tyrode solution containing ouabain, RCC in the presence of digitoxin reached peak amplitudes more rapidly, but elicited reduced peak amplitude values. Based on these findings, we suggest that: 1) the ability of the hydrophobic CS, digitoxin, but not the hydrophilic CS, ouabain, to produce a positive inotropic effect at 5°C, when the activity of the Na + pump is markedly reduced, is consistent with a mechanism other than Na + pump inhibition and involves an intracellular location; and 2) the diminished RCC observed in the presence of the hydrophobic CS, digitoxin, indicate that this alternative mechanism may involve effects on the SR Ca 2+ release channel.

Preservation of NO production by statins in the treatment of heart failure.

Because statins promote endogenous nitric oxide (NO) production in vessels by increasing endothelial nitric oxide synthase (eNOS), we evaluated the clinical benefit and efficiency of simvastatin in preventing the decrease in NO control of coronary blood flow (CBF), NO regulation of myocardial oxygen consumption (MVO(2)) and decreased nitrite production in coronary microvessels, associated with pacing-induced heart failure (HF). Dogs (n=17) were instrumented for measurement of coronary blood flow and left ventricular end diastolic pressure (LVEDP). HF was induced by pacing. Ten dogs were given simvastatin 20 mg/kg/day orally (HF+SIMVA) from the 10th day of pacing. HF+SIMVA had a lower LVEDP at 4 weeks of pacing (18+/-1 vs. 25+/-1 mm Hg, p<0.05), and the NO-dependent coronary vasodilation to veratrine was preserved compared to HF (p<0.05). In coronary microvessels, SIMVA potentiated nitrite production compared to HF (p<0.05) and enhanced the NO-dependent decrease in MVO(2) in cardiac tissue in response to 10(-4) mol/l bradykinin, which was markedly blunted in HF (p<0.05). Using Western blotting, there was a reduction in eNOS protein during HF that was preserved at 4-5 weeks of pacing during treatment with SIMVA. Simvastatin maintained NO production by coronary vessels and NO bioactivity during pacing-induced dilated cardiomyopathy. Targeting the endothelium, which participates in the control of myocardial metabolism by NO, may be an important mechanism of action of statins in the treatment of heart failure.

New technique for measurement of left ventricular pressure in conscious mice.

Concern about the effects of anesthesia on physiological measurements led us to develop methodology to assess left ventricular (LV) pressure in conscious mice. Polyethylene-50 tubing filled with heparinized saline was implanted in the LV cavity through its apex via an abdominal approach and exteriorized to the back of the animal. This surgery was done under anesthesia with either an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (5 mg/kg) (K+X) in 11 mice or isoflurane (ISF; 1.5 vol%) by inhalation in 14 mice. Postoperatively, mice were trained daily to lie quietly head first in a plastic cone. LV pressure, the first derivative of LV pressure (dP/dt), and heart rate (HR) in the conscious state were compared between the two groups at 3 days and 1 wk after recovery from surgery using a 1.4-Fr Millar catheter inserted into the LV through the tubing, with the mice lying quietly in the plastic cone. Acutely during anesthesia, K+X decreased HR (from 698 to 298 beats/min), LV systolic pressure (from 107 to 65 mmHg), and maximal dP/dt (dP/dt(max)) (from 15,724 to 4,445 mmHg/s), all P < 0.01. Similar but less marked negative chronotropic and inotropic effects were seen with ISF. HR and dP/dt(max) were decreased significantly in K+X mice 3 days after surgery compared with those anesthetized with ISF (655 vs. 711 beats/min, P < 0.05; 14,448 vs. 18,048 mmHg/s, P < 0.001) but increased to the same level as in ISF mice 1 wk after surgery. In ISF mice, recovery of function occurred rapidly and there were no differences in LV variables between 3 days and 1 wk. LV pressure and dP/dt can be measured in conscious mice with a micromanometer catheter inserted through tubing implanted permanently in the LV apex. Anesthesia with either K+X or, to a lesser extent, ISF, depressed LV function acutely. This depression of function persisted for 3 days after surgery with K+X (but not ISF) and did not recover completely until 1 wk postanesthesia.

Cariporide enhances lactate clearance upon reperfusion but does not alter lactate accumulation during global ischaemia

Cariporide (HOE 642) inhibits the Na+/H+ exchanger and would be expected to reduce lactate accumulation during ischaemia and stimulate lactate/H+ co-transporter upon reperfusion. The aim of this study was to determine the effect of cariporide on lactate production during global ischaemia and release during reperfusion. Guinea-pig hearts perfused in the Langendorff mode were exposed to 45 min global ischaemia and 30 min reperfusion with or without cariporide (5 or 10 micromol/l). Cardiac function was assessed by measurement of left ventricular developed pressure (LVDP). Lactate and pH were measured in coronary effluent before ischaemia and throughout reperfusion. Tissue metabolites (lactate, adenine nucleotides, guanine nucleotides and purine) were measured in ventricular biopsy samples collected at the beginning and end of ischaemia. Cariporide significantly improved recovery of LVDP (from 66% for control to 88% and 93% for 5 and 10 micromol/l cariporide, respectively). During ischaemia, only 10 micromol/l cariporide produced a small (10%) but significant preservation of ATP and GTP compared to control. This was associated with significant reduction (25%) in ischaemic contracture. Cariporide did not influence lactate accumulation during ischaemia but significantly increased lactate efflux (18%) during the first 60 s of reperfusion. In conclusion, cariporide does not alter lactate accumulation during ischaemia but enhances lactate efflux upon reperfusion, which may have implications for its cardioprotective action.

Detection of a pseudonormal mitral inflow pattern: an echocardiographic and tissue Doppler study.

The aim of this study was to assess the ability of several echocardiographic and tissue Doppler imaging (TDI) derived parameters to improve the noninvasive diagnosis of a pseudonormal mitral inflow pattern. Ninety-eight consecutive patients with age-related normal transmitral Doppler profile underwent echocardiography including TDI and measurement of left ventricular end-diastolic pressure (LVEDP) using fluid-filled catheters. Peak transmitral velocities were determined at rest (E, A) and during the strain phase of a Valsalva maneuver. The difference in duration between the pulmonary venous retrograde velocity and the transmitral A-velocity (PVR-A) was calculated from pulsed Doppler recordings. Propagation velocity of the early mitral inflow (VP) was determined by color M-mode. Early diastolic peak mitral annulus velocities (E') and the early diastolic transmyocardial velocity gradient of the posterior basal wall (MVG) were obtained by TDI. Fifty-two patients presented with normal diastolic function (group I: LVEDP9.5 +/- 3 mm Hg, E/A1.1 +/- 0.19), while pseudonormalization, defined as LVEDP 15 mm Hg and E/A > 0.9, was found in 46 patients (group II: LVEDP23 +/- 7 mm Hg, E/A1.43 +/- 0.83). The coefficient of linear correlation (r) and the area under ROC - curve (AUC) to predict LVEDP values 15 mm Hg were maximal for the index PVR-A (AUC = 0.92, r = 0.77), followed byE/E' (AUC = 0.80, r = 0.46), MVG (AUC = 0.65, r = 0.33) and E/VP (AUC = 0.69, r = 0.30), P < 0.01, whereas the decrease in E/A ratio during Valsalva maneuver failed to reach significance. Similar results were observed when echocardiographic parameters were used to estimate the left ventricular diastolic pressure before atrial contraction. PVR-A enabled the most accurate estimation of LVEDP. TDI-derived indices E/E' and MVG are also reliable alternatives superior to the classical Valsalva maneuver to detect a pseudonormal transmitral Doppler profile.

Effects of burst stimulation during ventricular fibrillation on cardiac function after defibrillation.

The purpose of defibrillation is to rapidly restore blood flow and tissue perfusion following ventricular fibrillation (VF) and shock delivery. We tested the hypotheses that 1) a series of 1-ms pulses of various amplitudes delivered before the defibrillation shock can improve hemodynamics following the shock, and 2) this hemodynamic improvement is due to stimulation of cardiac or thoracic sympathetic nerves. Ten anesthetized pigs received a burst of either 15 or 30 1-ms pulses (0.1-10 A in strength) during VF, after which defibrillation was performed. ECG, arterial blood pressure, and left ventricular (LV) pressure were recorded. Defibrillation shocks and burst pulses were delivered from a right ventricular coil electrode to superior vena cava coil and left chest wall electrodes. Sympathetic blockade was induced with 1 mg/kg timolol and trials were repeated. The first half of this protocol was repeated in two animals that were pretreated with reserpine. Heart rate (HR) after 1-, 2-, 5-, and 10-A pulses was significantly higher than after control shocks without preceding pulse therapy. Mean and peak LV pressure measurements increased 38 and 72%, respectively, following shocks preceded by 5- and 10-A pulses compared with shocks preceded by no burst pulses. Mean and peak arterial pressures increased 36 and 43%, respectively, following shocks preceded by 5- and 10-A pulses compared with shocks preceded by no burst pulses. After beta-blockade, HR, mean and peak arterial pressures, and mean LV pressure were not significantly different after pulses of any strength compared with control shocks. LV peak pressure following the 10-A pulses was significantly higher than with no burst pulses but was significantly lower than the response to the 10-A pulses delivered without beta-blockade. HR, mean and peak arterial pressures, and mean and peak LV pressure responses after 15 or 30 5- or 10-A pulses were similar to the responses to the same pulses after beta-blockade. We conclude that a burst of 15-30 1-ms pulses delivered during VF can increase HR, arterial pressure, and LV pressure following defibrillation. beta-Blockade or reserpine pretreatment prevents most of this postshock increase in HR, arterial pressure, and LV pressure.

Short-term administration of ethanol does not affect functional recovery from myocardial stunning in awake dogs.

Chronic ingestion of small doses of ethanol protects the myocardium from ischemic damage. It was demonstrated that short-term administration of ethanol (SAE) enhances the recovery of stunned myocardium in acutely instrumented, anesthetized dogs. It is unclear whether this beneficial effect of SAE also occurs in awake dogs. Therefore, we investigated the effects of SAE on regional myocardial stunning in awake dogs. Thirty-six dogs were chronically instrumented for measurement of heart rate, left atrial, aortic, and left ventricular pressure, left systolic ventricular contactility (dP/dt(max)) and diastolic ventricular function (dP/dt(min)), and regional myocardial wall-thickening fraction (WTF). Occluders around the left anterior descending (LAD) artery allowed the induction of reversible ischemia in the LAD-perfused myocardium. The dogs were assigned to one of three groups that differed in the dose of ethanol administered in the ethanol experiment (I, 0.125 g/kg [n = 12]; II, 0.25 g/kg [n = 12]; III, 0.5 g/kg [n = 12]). In each group, the dogs underwent two ischemic episodes (randomized crossover fashion; separate days): 10 min of LAD occlusion after the application of ethanol IV over 30 min (ethanol group) and without ethanol (control). WTF and hemodynamic variables were measured at baseline and at predetermined time points until complete recovery of myocardial stunning occurred. LAD-ischemia led to a significant decrease of LAD-WTF in all groups. There was no difference in WTF and hemodynamic variables with or without SAE during reperfusion. We conclude that SAE (0.125 g/kg, 0.25 g/kg, and 0.5 g/kg) does not significantly affect myocardial stunning in conscious dogs. In contrast to previous experiments in anesthetized dogs, short-term administration of ethanol does not alter myocardial stunning in conscious dogs.

Postextrasystolic contractility normally decays in alternans in canine in situ heart.

We have reported that the postextrasystolic (PES) potentiation of left ventricular (LV) contractility usually decays in alternans at heart rates above 80-100 beats/min in the canine excised, cross-circulated heart. We examined whether the PES contractility would also decay in alternans even in the canine in situ heart presumably more physiological than the excised heart. In anesthetized, ventilated, and open-chest mongrel dogs, we measured LV pressure and volume with a micromanometer and a conductance catheter cannulated into the LV and obtained LV end-systolic maximum elastance (E(max)) as the reasonably load-independent contractility index. We inserted an extrasystole followed by a compensatory pause into steady-state regular beats at heart rates above 90 beats/min and analyzed the PES decay pattern of E(max). We found that E(max) potentiated in the first PES beat decayed in alternans within 5-6 PES beats. This indicates that PES contractility also decays in alternans in the normal canine in situ heart.

A role for the aryl hydrocarbon receptor in cardiac physiology and function as demonstrated by AhR knockout mice.

The aryl hydrocarbon receptor (AhR), a ligand activated transcription factor, is the receptor for the polycyclic aromatic hydrocarbons found in tobacco smoke, polychlorinated biphenyls, and the environmental pollutant, dioxin. To better understand the role of the AhR in the heart, echocardiography, invasive measurements of aortic and left ventricular pressures, isolated working heart preparations, as well as morphological and molecular analysis were used to investigate the impact of AhR inactivation on the mouse heart using the AhR knockout as a model. Cardiac hypertrophy is an early phenotypic manifestation of the AhR knockout. Although the knockout animals were not hypertensive at the ages examined, cardiomyopathy accompanied by diminished cardiac output developed. Despite the structural left ventricular remodeling, the hearts of these animals exhibit minimal fibrosis and do not have the expected increases in surrogate molecular markers of cardiac hypertrophy. The anatomic remodeling without typical features of molecular remodeling is not consistent with hypertrophic growth secondary to pressure or volume overload, suggesting that increased cardiomyocyte size may be a direct consequence of the absence of the AhR in this cell type.